The reduction of C4(5) double bond of testosterone has been recognized as one of the important metabolic events in tissues that respond to androgens. This reaction appears to be essential for androgen activation which is followed by a series of biochemical events and physiological changes that are observed in androgen sensitive tissue. The fibroadenoma of the human breast has been demonstrated to exhibit a marked degree of conversion of testosterone to 5 alpha dihydrotestosterone, strongly suggesting a role for androgens in the pathogenesis of that neoplasm. The importance of the androgens in the development of benign prostatic hyperplasia (BPH) is also known. Because of histologic similarities between the fibroadenoma of the breast, certain type of BPH nodules and the uterine leiomyomata, studies have been undertaken to clarify the role of androgens in the normal human uterus, uterine leiomyoma, uterine carcinoma, and uterine sarcoma. It is the objective of this grant proposal to ascertain the extent of conversion of testosterone and androstenedione to various active androgenic and estrogenic metabolities by the uterine tissues in normal and neoplastic states. If the preliminary studies are borne out, then antiandrogens, in conjunction with surgical procedures, may be useful as therapeutic modalities in metastatic carcinoma and sarcoma. Antiandrogens could perhaps also be considered instead of surgery in the treatment of uterine leiomyomata.